DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Arguments
Applicant's arguments filed 4/23/2026 have been fully considered but they are not persuasive.
First, Applicant’s arguments as they relate to amended claim 1 is not persuasive since there are new grounds of rejection for claim 1 under 35 USC 102(a)(1) over Brown (US 3,833,509) or under 35 USC 103 over Oelsner.
Although, Czerwinski is still cited with respect to claim 10 and acetate eluant, the Office maintains that even though Czerwinski relates to an improvement by modifying titanium with phosphate, Czerwinski is still relevant to eluants for thorium daughter isotopes. The Office notes that Czerwinski teaches that phosphate modified TiO2 materials are superior to untreated TiO2 but Czerwinski also teaches that TiO2 is an improved option as a generator for Ac-225 providing all of the necessary qualities that are desired in the generator.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Brown (US 3,833,509).
First, “equilibrate” in claim 1 is broadly interpreted as referring to allowing some amount of daughter isotope to build up and not any particular amount or fully saturated amount or secular equilibrium. Support for this interpretation is in the Specification as filed at [36] where equilibration time is less than less than full saturation.
Brown teaches a method for radionuclide generation comprising:
Contacting a chromatographic alumina column (i.e., inorganic metal oxide ion exchange column) with Mo-99 using a sodium molybdate solution (i.e., contacting with a parent isotope);
Allowing the column to stand for a period of 30 minutes (i.e., allowing the column to equilibrate between parent and daughter isotopes);
Eluting Tc-99m for five successive days (i.e., eluting a daughter isotope and repeating the equilibration and eluting steps (see
Therefore, Brown teaches a method comprising all of the limitations of claim 1.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically taught as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 4, 9, 11, 21, 23, and 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Oelsner (US 2013/0220928).
Oelsner teaches a method for isolating a daughter radioisotope that is produced by a parent isotope by radioactive decay comprising:
Adsorbing a parent isotope onto particles of an inorganic metal oxide to produce inorganic metal oxide particles comprising adsorbed parent radioisotope (i.e., contacting an inorganic metal oxide with a parent isotope);
Allowing a portion of the parent radionuclide to decay to the daughter isotope (i.e., allowing the column to equilibrate between parent and daughter isotopes);
Eluting a solution of the daughter radioisotope from the inorganic metal oxide from the inorganic metal oxide particles comprising absorbed parent radioisotope (see [0035-0038]).
Where there are multiple elution (i.e., where equilibration and elution steps are repeated) (see Figures 4-5).
Oelsner further teaches the radioisotope generator comprising a chromatography column packed with the inorganic metal oxide particles (i.e., an inorganic metal oxide ion-exchange column) (see [0058]). Oelsner further teaches the inorganic metal oxide comprising titanium oxide, aluminum oxide, zirconium oxide or silicon dioxide (see [0079]). Oelsner does not disclose the inorganic metal oxide particles comprising phosphorus.
It would have been obvious to one of ordinary skill in the art at the time of filing of the invention to perform the process for producing daughter isotope where the inorganic metal oxide is any metal oxide selected from titanium oxide, aluminum oxide, zirconium oxide or silicon dioxide, as taught by Oelsner including titanium oxide, aluminum oxide, and zirconium oxide since Oelsner suggests that each are suitable for producing a daughter radioisotope generator.
Regarding claim 4, Oelsner teaches a process comprising eluting with hydrochloric acid (see [0096]).
Regarding claim 9, Oelsner teaches a parent/daughter radioisotope pair comprising Th-228/Bi-212 (i.e., a parent with an atomic number of 90 and a daughter with an atomic number of 83) (see [0080]).
Regarding claim 11, Oelsner teaches a method where the daughter isotope is eluted with 0.1 N HCl (i.e., a fluid having a pH of 1).
Regarding claim 21, Oelsner teaches a method for isolating a daughter radioisotope that is produced by a parent isotope by radioactive decay comprising:
Adsorbing a parent isotope onto particles of an inorganic metal oxide to produce inorganic metal oxide particles comprising adsorbed parent radioisotope (i.e., contacting an inorganic metal oxide with a parent isotope);
Allowing a portion of the parent radionuclide to decay to the daughter isotope (i.e., allowing the column to equilibrate between parent and daughter isotopes);
Eluting a solution of the daughter radioisotope from the inorganic metal oxide from the inorganic metal oxide particles comprising absorbed parent radioisotope (see [0035-0038]).
Where there are multiple elution (i.e., where equilibration and elution steps are repeated) (see Figures 4-5).
Oelsner further teaches the radioisotope generator comprising a chromatography column packed with the inorganic metal oxide particles (i.e., an inorganic metal oxide ion-exchange column) (see [0058]). Oelsner further teaches the inorganic metal oxide comprising titanium oxide, aluminum oxide, zirconium oxide or silicon dioxide (see [0079]). Oelsner does not disclose the inorganic metal oxide particles comprising phosphorus.
It would have been obvious to one of ordinary skill in the art at the time of filing of the invention to perform the process for producing daughter isotope where the inorganic metal oxide is any metal oxide selected from titanium oxide, aluminum oxide, zirconium oxide or silicon dioxide, as taught by Oelsner including zirconium oxide as claimed since Oelsner suggests that each are suitable for producing a daughter radioisotope generator.
Regarding claim 23, Oelsner teaches a process comprising eluting with hydrochloric acid (see [0096]).
Regarding claim 26, Oelsner teaches an inorganic metal oxide free of phosphorus or carbon.
Claim(s) 2, 22 and 29 is/are rejected under 35 U.S.C. 103 as being unpatentable over Oelsner as applied to claim 1 or 21, and in further view of Westrom et al (Ra‐224 labeling of calcium carbonate microparticles for internal α‐therapy: Preparation, stability, and biodistribution in mice, J Labelled Compounds and Radiopharmaceuticals, (2018);61:472-486).
As applied to claim 1 or 21, Oelsner teaches a process for generating a daughter isotope comprising all of the limitations of the claims.
Regarding claims 2 and 22, Oelsner teaches a method where the parent isotope is Thorium-228 (see [0080]). Oelsner does not teach a method where the daughter is radium and the equilibrate step has a duration between 2 days and 2 months.
Westrom teaches Radium-224 as an α-emitter is attractive for radionuclide therapy for bone seeking applications of cancer treatment (see Abstract and Introduction). Westrom further teaches a Radium-224 generator based on Thorium-228 (see Page 475, 2.2. Preparation of 224Ra generator based on 228Th). Westrom further teaches that a pure source of 224Ra reaches equilibrium conditions after 2 days (see Page 475-476, 2.4. Radioactivity Measurements). It would have been obvious to one of ordinary skill in the art at the time of filing of the invention to use the generator as taught by Oelsner where the parent/daughter pair comprises Th-228 and Ra-224 and the equilibrium period is 2 days as taught by Westrom since Ra-224 is attractive for cancer therapy.
Regarding claim 29, Westrom teaches the parent/daughter isotope pair comprising Th-228/Ra-224.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Oelsner as applied to claim 1, and in further view of Quirico et al (US 8,708,352).
As applied to claim 1, Oelsner teaches a method for generating daughter isotopes, the method comprising contacting an inorganic metal oxide ion exchange column with a parent isotope to create a column-parent isotope construct, allowing the column to equilibrate between the parent and daughter isotopes; eluting the daughter isotopes from the column; and repeating steps b and c.
Oelsner does not a method comprising in between elution steps, subjecting the construct to processes including drying, transport, sequestration in radiation proof containers, delivery to end users of the daughter isotope, and combinations thereof.
Quirico teaches an infusion system comprising a shielding assembly comprising a compartment for containing a radionuclide generator (see Col 6, Ln 60-67), the system comprising wheels to make the system mobile (see Col 3, LN 37-39), and a method of operation wherein after the elution process for patent infusion the system can be moved to a new site if the generator is not depleted (see Col 16, Ln 1-2). It would have been obvious to one of ordinary skill in the art at the time of filing of the invention to perform a method as taught by Oelsner where the construct is subjected to transport to a new site after elution as taught by Quirico so that the generator can be used if the generator is not depleted as suggested by Quirico.
Claims 7, 12, 27, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Oelsner as applied to claim 1 or 21 and in further view of Westrom and Paris et al (US 2018/0233243).
As applied to claim 1, Oelsner teaches a method for generating daughter isotopes, the method comprising contacting an inorganic metal oxide ion exchange column with a parent isotope to create a column-parent isotope construct, allowing the column to equilibrate between the parent and daughter isotopes; eluting the daughter isotopes from the column; and repeating steps b and c.
As applied to claim 21, Oelsner further teaches zirconia.
Regarding claim 7 and 27, Oelsner further teaches a method where the parent isotope is thorium-228 (see [0080]). Oelsner does not specifically teach wherein the daughter isotope is radium and the equilibration step having a duration between 5 and 14 days.
Regarding a parent/daughter isotope pair of thorium and radium, Westrom teaches Radium-224 as an α-emitter is attractive for radionuclide therapy for bone seeking applications of cancer treatment (see Abstract and Introduction). Westrom further teaches a Radium-224 generator based on Thorium-228 (see Page 475, 2.2. Preparation of 224Ra generator based on 228Th). Westrom further teaches that a pure source of 224Ra reaches equilibrium conditions after 2 days (see Page 475-476, 2.4. Radioactivity Measurements). It would have been obvious to one of ordinary skill in the art at the time of filing of the invention to use the generator as taught by Oelsner where the parent/daughter pair comprises Th-228 and Ra-224 as taught by Westrom since Ra-224 is attractive for cancer therapy.
Regarding a equilibrate step having a duration of 5 days and 14 days, Paris teaches a method for generating daughter isotopes in a radioisotope generator having a stationary phase comprising titanium oxide (see [0001]). Paris teaches a method where parent isotope is initially loaded on the stationary phase and the daughter radioisotope is continuously produced by the disintegration of the parent isotope for use in nuclear medicine, biomedical research and diagnostic (see [0015] to [0019]). Paris teaches eluting the daughter radioisotope when the amount of daughter radioisotope is estimated to be sufficient (see [0019]). Paris therefore suggests that the time before elution of a column-parent isotope construct (i.e., the equilibration step) is a results-effective variable on the amount of daughter isotope eluted and that the amount of daughter isotope.
It is well established that optimization within prior art conditions or through routine experimentation in the pertinent art are unpatentable as obvious if a person of ordinary skill in the art has a motivation to optimize and a reasonable expectation of success. Here, a person of ordinary skill in the art would be motivated to provide for a sufficient equilibration time to produce sufficient daughter isotope for the end-use and would also have a reasonable expectation of success because Paris suggests that the amount of daughter isotope required is an estimable amount. Westrom also teaches a method where the daughter radionuclides are used as radiotherapeutic agents in the treatment of malignancies (see Introduction). It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to improve upon the equilibrate step of 2 days as taught by Czerwinski to determine optimum or workable range including a claimed range of 5 to 14 days as a matter of routine optimization for constant amounts of Radium-224 needed for the specific nuclear medical use or research and diagnostic.
Regarding claims 12 and 30, Oelsner and Westrom does not disclose a method wherein the equilibration step has a duration to allow for daughter isotope saturation rates of between 1 percent and 50 percent. It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to improve upon the equilibrate step of 2 days as taught by Czerwinski to determine optimum or workable duration including a claimed duration to allow for daughter isotope saturation rates of between 1 percent and 50 percent as a matter of routine optimization for constant amounts of Radium-224 required for the specific nuclear medical use or research and diagnostic.
Claims 8 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Oelsner as applied to claim 1 or 21 and in further view of Shanks et al (US 2012/0285294).
As applied to claim 1, Oelsner teaches a method for generating daughter isotopes, the method comprising contacting an inorganic metal oxide ion exchange column with a thorium parent isotope to create a column-parent isotope construct, allowing the column to equilibrate between the parent and daughter isotopes; eluting the daughter isotopes from the column; and repeating steps b and c.
As applied to claim 21, Oelsner further teaches zirconia.
Regarding claim 8 and 28, Oelsner does not specifically disclose a method the equilibration step is selected based on decay rates of the parent isotope and daughter isotope.
Shanks teaches a multiple generator elution system comprising forming an elution schedule based on using calculations taking into account parent nuclide half-life and decay equation and the daughter nuclide half-life and decay equation (see [0039]). Shanks teaches a system achieving workflow efficiencies and matching demand with supply (see [0031]). It would have been obvious to one of ordinary skill in the art at the time of filing of the invention perform the method for generating isotopes as taught by Oelsner and to set the equilibrate step and elution (i.e., elution schedule) and use the parent and daughter isotope half-life and decay equation (decay rates) as taught by Shanks, in order to form workflow efficiencies and match the demand with the supply of daughter isotopes.
Claims 10 are rejected under 35 U.S.C. 103 as being unpatentable over Oelsner as applied to claim 1, and in further view of Czerwinski et al (US 2022/0339292).
As applied to claim 1, Oelsner teaches a process for generating a daughter isotope comprising all of the limitations of the claims.
Regarding claim 10, Oelsner does not teach wherein the daughter isotope is eluted when the column is contacted with an acetate solution.
Czerwinski teaches a method for generating Ac and Ra (i.e., a daughter isotope), the method comprising:
Contacting a solution including Th with a titania ion exchange column to produce a Th-loaded titania material (i.e., contacting an inorganic metal oxide ion exchange column with parent isotope to create a column-parent isotope construct);
Eluting the Th-loaded material with a wash solution to produce an eluted solution containing eluted compounds including Ac and Ra where different eluants may be used and where as an example eluant includes acetic acid (HOA)/sodium acetate (NaOA) solution (i.e., Eluting the daughter isotope from the column); (see [0027] and [0035-0039]).
Where eluting/milking is performed periodically on a schedule or at random intervals based on Ac need (i.e., Repeating step b) (see [0039].
Czerwinski teaches that acetate is unlikely to interfere with Th binding to the TiO2 and minimizes the breakthrough of Th from the column (see [0084-0086]). It would have been obvious to one of ordinary skill in the art at the time of filing of the invention to perform the method as taught by Oelsner where the eluant comprises acetate as taught by Czerwinski to prevent breakthrough of thorium when eluting daughter isotopes.
Allowable Subject Matter
Claims 24-25 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL FORREST whose telephone number is (571)270-5833. The examiner can normally be reached Monday-Friday (10AM-6PM).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sally A Merkling can be reached at (571)272-6297. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MICHAEL FORREST/Primary Examiner, Art Unit 1738
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